Critical Limb Ischemia as a Rare Presentation of Malignant Solitary Fibrous Tumor of the Pleura.

BACKGROUND Solitary fibrous tumor (SFT) of the pleura is a rare fibroblastic neoplasm. It is commonly found incidentally on imaging and is usually benign but has significant potential to recur as a malignant tumor. Patients present asymptomatically or with pulmonary symptoms such as cough or shortness of breath. Cardiac invasion of an SFT can create an avenue for peripheral tumor embolization and critical limb ischemia, as in this case report. There is no prior published report of recurring malignant SFT presenting as critical limb ischemia. CASE REPORT We report a rare presentation of malignant SFT recurrence in a 57-year-old woman with critical limb ischemia of both lower extremities secondary to bilateral tumor emboli. The patient's primary tumor was treated with surgical resection alone. Upon recurrence, the tumor growth was so extensive that it was no longer amenable to surgical resection at the time of her critical limb ischemia. The patient presented with bilateral numbness and tingling, without any pulmonary symptoms. CONCLUSIONS Although it is sporadic, clinicians should know that an aggressive malignant SFT can embolize and present as critical limb ischemia. The possibility of tumor emboli provides a pressing reason to surgically resect SFT masses in their early stages before any cardiac invasion.

18F-FES PET/CT Improves the Detection of Intraorbital Metastases in Estrogen-Receptor-Positive Breast Cancer: Two Representative Cases and Review of the Literature.

Orbital metastases are a rare but life-altering complication in cancer. Most commonly seen in breast cancer, metastases to the optic nerves or extraocular muscles can have a devastating impact on visual acuity and quality of life. Hormone receptor status plays a central role in metastatic breast cancer treatment, with endocrine therapy often representing first-line therapy in hormone-receptor-positive cancers. Staging and treatment response evaluation with positron emission tomography (PET) computed tomography (CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) is limited by high physiologic uptake in the intracranial and intraorbital compartments. Thus, traditional staging scans with 18F-FDG PET/CT may under-detect intraorbital and intracranial metastatic disease and inaccurately evaluate active metastatic disease burden. In comparison, 18F-fluoroestradiol (18F-FES) is a novel estrogen-receptor-specific PET radiotracer, which more accurately assesses the intracranial and intraorbital compartments in patients with estrogen-receptor-positive (ER+) cancers than 18F-FDG, due to lack of physiologic background activity in these regions. We present two cases of breast cancer patients with orbital metastases confirmed on MR imaging who underwent PET/CT imaging with 18F-FES and 18F-FDG. Multimodality imaging with 18F-FES PET/CT offers higher detection sensitivity of orbital metastases, compared with traditional 18F-FDG PET/CT imaging, and can improve the assessment of treatment response in patients with estrogen-receptor-positive (ER+) cancers.

Pancreatic Adenocarcinoma Invasiveness and the Tumor Microenvironment: From Biology to Clinical Trials.

Pancreatic adenocarcinoma (PDAC) originates in the glandular compartment of the exocrine pancreas. Histologically, PDAC tumors are characterized by a parenchyma that is embedded in a particularly prominent stromal component or desmoplastic stroma. The unique characteristics of the desmoplastic stroma shape the microenvironment of PDAC and modulate the reciprocal interactions between cancer and stromal cells in ways that have profound effects in the pathophysiology and treatment of this disease. Here, we review some of the most recent findings regarding the regulation of PDAC cell invasion by the unique microenvironment of this tumor, and how new knowledge is being translated into novel therapeutic approaches.

Development and application of stable phantoms for the evaluation of photoacoustic imaging instruments.

Photoacoustic imaging combines the high contrast of optical imaging with the spatial resolution and penetration depth of ultrasound. This technique holds tremendous potential for imaging in small animals and importantly, is clinically translatable. At present, there is no accepted standard physical phantom that can be used to provide routine quality control and performance evaluation of photoacoustic imaging instruments. With the growing popularity of the technique and the advent of several commercial small animal imaging systems, it is important to develop a strategy for assessment of such instruments. Here, we developed a protocol for fabrication of physical phantoms for photoacoustic imaging from polyvinyl chloride plastisol (PVCP). Using this material, we designed and constructed a range of phantoms by tuning the optical properties of the background matrix and embedding spherical absorbing targets of the same material at different depths. We created specific designs to enable: routine quality control; the testing of robustness of photoacoustic signals as a function of background; and the evaluation of the maximum imaging depth available. Furthermore, we demonstrated that we could, for the first time, evaluate two small animal photoacoustic imaging systems with distinctly different light delivery, ultrasound imaging geometries and center frequencies, using stable physical phantoms and directly compare the results from both systems.

A c-Myc activation sensor-based high-throughput drug screening identifies an antineoplastic effect of nitazoxanide.

Deregulation of c-Myc plays a central role in the tumorigenesis of many human cancers. Yet, the development of drugs regulating c-Myc activity has been challenging. To facilitate the identification of c-Myc inhibitors, we developed a molecular imaging sensor-based high-throughput screening (HTS) system. This system uses a cell-based assay to detect c-Myc activation in a HTS format, which is established from a pure clone of a stable breast cancer cell line that constitutively expresses a c-Myc activation sensor. Optimization of the assay performance in the HTS format resulted in uniform and robust signals at the baseline. Using this system, we conducted a quantitative HTS against approximately 5,000 existing bioactive compounds from five different libraries. Thirty-nine potential hits were identified, including currently known c-Myc inhibitors. There are a few among the top potent hits that are not known for anti-c-Myc activity. One of these hits is nitazoxanide, a thiazolide for treating human protozoal infections. Validation of nitazoxanide in different cancer cell lines revealed a high potency for c-Myc inhibition with IC50 ranging between 10 and 500 nmol/L. Oral administration of nitazoxanide in breast cancer xenograft mouse models significantly suppressed tumor growth by inhibition of c-Myc and induction of apoptosis. These findings suggest a potential of nitazoxanide to be repurposed as a new antitumor agent for inhibition of c-Myc-associated neoplasia. Our work also demonstrated the unique advantage of molecular imaging in accelerating discovery of drugs for c-Myc-targeted cancer therapy.